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Thorac Cardiovasc Surg 2018; 66(01): 063-070
DOI: 10.1055/s-0037-1607051
Original Basic Science
Georg Thieme Verlag KG Stuttgart · New York

Localization of Exogenous Mesenchymal Stem Cells in a Pig Model of Lung Transplantation

Tanja Piatkowski
1   Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
,
Christina Brandenberger
1   Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
2   Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy), Hannover, Germany
,
Parwis Rahmanian
3   Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Kerpener Str. 61, 50924 Cologne, Germany
,
Yeong-Hoon Choi
3   Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Kerpener Str. 61, 50924 Cologne, Germany
,
Mohamed Zeriouh
3   Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Kerpener Str. 61, 50924 Cologne, Germany
,
Anton Sabashnikov
3   Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Kerpener Str. 61, 50924 Cologne, Germany
,
Thorsten Wittwer
3   Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Kerpener Str. 61, 50924 Cologne, Germany
,
Thorsten C. W. Wahlers
3   Department of Cardiothoracic Surgery, Heart Center, University of Cologne, Kerpener Str. 61, 50924 Cologne, Germany
,
Matthias Ochs
1   Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
2   Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy), Hannover, Germany
4   Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany
,
Christian Mühlfeld
1   Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
2   Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy), Hannover, Germany
4   Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany
› Author Affiliations
Further Information

Publication History

22 May 2017

16 August 2017

Publication Date:
09 October 2017 (online)

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Abstract

Background Mesenchymal stem cells (MSCs) have a great potential for the treatment of acute lung injury. This study provides a detailed immunohistochemical and stereological analysis of the localization and distribution of exogenous MSC in a pig model of lung transplantation after intravascular or endobronchial application.

Methods MSC derived from human bone marrow were labeled by DiI and administered intravascularly or endobronchially to the lungs of donor pigs after a period of 3 hours warm and 3 hours cold ischemia. The left lung was transplanted to a recipient pig and reperfused for 4 hours before fixation. The right donor lung was fixed for microscopic analysis directly after the ischemia time.

Results After both administration routes, a similar number of exogenous MSC was found in the lungs. Within each animal, the heterogeneity of MSC distribution was high both with respect to left and right lung as well as to the different lobes of each lung. After endobronchial application, MSC were found in alveolar and bronchial/bronchiolar lumen, whereas after intravascular administration, they were mainly observed in blood vessels.

Conclusion Although the administration of exogenous MSC is possible by endobronchial or intravascular application, it yields a heterogeneous distribution in the lungs which may warrant strategies to improve a more homogeneous distribution.

Keywords

lung transplantation - stem cells - cell culture

Authors' Contributions

T.P. established the immunohistochemistry and performed parts of the quantitative analysis; C.B. performed parts of the quantitative analysis and prepared the data for publication; P.R., M.Z., and A.S. performed the surgical experiments; Y.H.C. contributed to the preparation of stem cells and to the concept and design of the study; T.W. contributed to the surgical experiments and to the concept and design of the study; T.C.W.W contributed to the concept and design of the study; M.O. contributed to the concept and design of the study; C.M. contributed to the concept and design of the study, performed parts of the quantitative analysis, and wrote major parts of the article. All authors contributed to the critical interpretation of the results and to the critical revision of the article.